Dry skin or xerosis is a common condition that frequently requires therapeutic intervention. Xerosis is characterized by aggregated desquamating corneocytes with the appearance of fine white scales; clinically, it is often accompanied by decreased mechanical flexibility of the stratum corneum, fine fissures, inflammation, and sensations of itching and burning. The condition is believed to stem from impaired water-binding capability in the stratum corneum. It is aggravated by exposure to low temperatures and low indoor humidity in winter months commonly found in northern climates. Furthermore, other adverse environmental conditions such as exposure to detergents and solvents, subclinical dyskeratotic disorders and age support the clinical manifestation of xerosis.
Numerous humidifying topical preparations containing emollients and humectants have been used over the years for the treatment of dry skin, as well as for more acute dermatological disorders including ichthyosis, psoriasis, actinic damage, eczema, and the like which exhibit dry skin symptoms. Many such preparations primarily affect the skin's outer layer, the stratum corneum, and act as a partial replacement for the damaged stratum corneum.
In addition to traditional topical treatment with emollients, preparations with physiologically active ingredients have been suggested for the treatment of dry skin. High concentrations of urea (10% or higher), for example, have been suggested for the therapy of ichthyosis and other hyperkeratotic conditions (Swanbeck, G., Acta Derm. Venereol. 48:123-127 (1968)); urea appeared to exhibit both a water-binding function and a keratolytic activity, though a double blind study was not carried out (ibid.). In a brief review, Ashton, et al., suggested that higher urea concentrations, i.e., 40% to 48%, were beneficial in a double blind study, and that the dermatological importance of urea may also stem from its generally accepted property of unfolding proteins, thus solubilizing and/or denaturing them (Ashton, H., et al., Br. J. Dermatol. 84:194-196 (1971)).
Van Scott and Yu suggested that alpha-hydroxy and alpha keto acids in concentrations up to 12% be used for the treatment of dry skin, ichthyosis, follicular hyperkeratosis and other conditions (Van Scott, E. J., and Yu, R. J., Cutis, 43:222-228 (1989)). Lactic acid and glycolic acid were especially preferred for dry skin and analogous conditions (ibid., page 222). However, compositions containing these acids exhibit a very acidic milieu at pH values smaller than 2. Repeated topical application of compositions with such low pH values irritates the skin. It is therefore necessary to use these alpha-hydroxy acids in neutralized or at least partially neutralized forms. Topical application of the sodium salts of lactic and glycolic acid were found by the same investigators to be ineffective. They subsequently suggested that lactic and glycolic acid be used with amphoteric compounds such as amino acids or peptides and/or that polymeric forms of the alpha-hydroxy acids be employed (U.S. Pat. No. 5,091,171 to Yu and Van Scott). Compositions of this type that contain ammonium lactate have been shown to be efficacious in the treatment of dry skin (Rogers, R. S., et al., J. Am. Acad. Dermatol. 21:714-1989 (1991)). A currently marketed product under this invention is LacHydrin.RTM. (Westwood-Squibb Pharmaceuticals). It contains 14.0% ammonium lactate (equivalent to 12% lactic acid). It must be dispensed in the United States as a prescription drug.
Blair reported some findings about the action of a Calmurid.TM. ointment containing lactic acid, betaine, and 10% urea in the treatment of ichthyosis (Blair, C., Br. J. Dermatol. 94:145-153 (1976)). However, both the ointment base alone and the ointment with the active ingredients were effective in reducing the thickness of the skin scales (ibid., on page 150), and apparently only 11 patients participated in the study. In a double-blind trial involving 55 patients, Calmurid.TM. cream was no more effective than aqueous cream in the treatment of hyperkeratosis (Martindale Pharmacopeia, 29th edition, citing Report No. 179 of the General Practitioner Research Group, Practitioner 210:294 (1973)).
Urea has been suggested as an ingredient of other topical preparations having other active ingredients including cetyl dimethicone copolyol and silicone (U.S. Pat. No. 5,162,378 to Guthauser) and hydrocortisones (e.g., Carmol.TM., Physicians' Desk Reference, 45th ed., 1991, page 2198). Unless special emulsifiers or ingredients are employed with silicones, however, it is difficult to use them because of the instability of emulsions containing them. Use of topical steroid compositions have been reported to be associated with adverse effects after longterm usage, including epidermal and dermal atrophy, decreased collagen synthesis and the hazard of systemic absorption (Cecil's Textbook of Medicine, 17th ed., W. B. Saunders Co., Philadelphia, 1985, pages 2240-2241).